1. Field of the Invention
The present invention relates to a composition for inhibiting growth of cancer stem cells, which includes an EXT1 (exostosin 1), LDHB(lactate dehydrogenase B), CD109 (Cluster of Differentiation 109), EFEMP2 (EGF-containing fibulin-like extracellular matrix protein 2), RASIP1 (Ras interacting protein 1), or SERPINE1 (serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1) gene expression inhibitor as an active ingredient, and a method for treating cancer using the same.
2. Discussion of Related Art
Breast cancer is the most common malignant tumor, killing approximately 40,000 females every year, and thus is very important to diagnose at an early stage. However, viability in patients is still not improved when cancer is severely advanced or metastasized, even when the cancer is treated using various anti-cancer agents already known in the related art.
That is, the cause of death is not due to incipient cancer, but mainly due to recurrence or metastasis of cancer. Generally, drug resistance and cancer stem cells cause such recurrence and metastasis. Doxorubicin is a representative chemical used to treat breast cancer, and serves to remove actively dividing and proliferating breast cancer cells. The chemical has several side effects. One of the side effects is that cells having resistance to the chemical appear. According to recent reports, it is known that cancer stem cells play an important role in building resistance to the chemical.
As a representative anti-cancer therapy, chemotherapy alone or in combination with other therapeutic methods such as radiotherapy has been used as the most efficient therapeutic method to treat cancer. However, although the medicinal effect of anti-cancer drugs in chemotherapy varies according to the ability of the drugs to kill cancer cells, there is a problem in that the drugs may kill normal cells as well as the cancer cells when the drugs are used.
A hypothesis that cancer stem cells (CSCs) are cancer cells having unlimited regenerative abilities and tumors originate from stem cells was confirmed with publication of an article showing that a group of cells having a probability of converting into cancer stem cells in acute myelogenous leukemia were implanted into immunosuppressed rats and human leukemia was reproduced in the rats in the late 90s. Since then, cancer stem cells have been proven to exist in breast cancer, and stem cells in solid carcinomas have been confirmed.
Various heterogeneities of malignant tumors are coincident with various differentiative characteristics of stem cells, and the drug resistance of cancer cells that is endlessly expressed regardless of a number of target treatments is coincident with basic characteristics of the stem cells. As a result, formation of tumors may be considered to be associated with the stem cells, and cancer stem cells may become a new field of targeted therapy.
A variety of therapeutic methods have been designed based on the cancer stem cell hypothesis. Among these, a widely known method is a method in which a self-renewal pathway of the cancer stem cells is used. In this therapy, it is important to target the self-renewal of cancer stem cells while maintaining the self-renewal of normal stem cells. For example, a notch signal travels by means of an enzyme referred to as gamma secretase. In this case, when an inhibitor against gamma secretase (i.e., a gamma secretase inhibitor) is used to treat breast cancer in which Notch1 is overexpressed, it is possible to achieve an anti-tumor effect. When a hedgehog signal system is targeted, the therapeutic method is reported to have an anti-cancer effect. When a hedgehog inhibitor, cyclopamine, is administered to an animal into which tumor has been xenografted, the tumor is dramatically contracted. In addition, the hedgehog inhibitor is reported to be associated with MAPK and JAK2/STAT3 signaling pathways.
However, there are many limitations on research on cancer stem cells so far, and the roles of cancer stem cells in formation and maintenance of tumor has yet to be clearly identified. To efficiently perform treatment that targets only cancer stem cells without causing damage to normal stem cells, knowledge and understanding of molecular biological characteristics important for maintenance and regulation of cancer stem cells or regulatory pathways are required.
Also, not much research on anti-cancer agents directly targeting cancer stem cells has been conducted so far. In the prior art, various types of research on inhibiting cancer stem cells or suppressing upstream signaling proteins in the cancer stem cells to inhibit cancer stem cells were conducted as experiments for directly inhibiting target genes in cancer stem cells. However, such targeting experiments have encountered difficulties due to mutations of tumor genes and proteins in many tumor patients.
Therefore, improving the selectivity of an anti-cancer drug to cancer stem cells is sure to enable drugs to be used in smaller quantities by enhancing the medical efficacy of drugs in chemotherapy. Accordingly, an improved approach to selective inhibition of the growth of cancer stem cells to treat and prevent cancer is required.